PARTICIPATION OF NICOTINAMIDE MONONUCLEOTIDE IN PYRIDINE NUCLEOTIDE SYNTHESIS IN TUMOR AND HOST LIVER

1967 ◽  
Vol 45 (3) ◽  
pp. 363-373 ◽  
Author(s):  
J. W. D. McDonald ◽  
H. B. Stewart
Keyword(s):  
Pyridine Nucleotide ◽  
Host Liver ◽  
Nucleotide Synthesis ◽  
Nicotinamide Mononucleotide ◽  
Ehrlich Ascites ◽  
Nad Synthesis ◽  
Ehrlich Ascites Cells ◽  
High Doses

Evidence is presented to show that nicotinamide-7-14C in low or high doses is incorporated into nicotinamide mononucleotide (NMN) by Ehrlich ascites cells and host liver in vivo. Nicotinamide mononucleotide formed from nicotinamide-7-14C has been isolated from incubations of Sephadex-treated extracts of ascites cell acetone powders with 5-phosphoribosyl-1-pyrophosphate and characterized by spectral and chemical analysis. The apparent Km and Vmax for NMN synthesis from nicotinamide have been determined. NMN-14C has been shown to form NAD-14C in the same extracts in the presence of ATP, and the apparent Vmax and Km of this process have been determined. The role of NMN in NAD synthesis is discussed.

THE MECHANISM OF PYRIDINE NUCLEOTIDE SYNTHESIS IN EHRLICH ASCITES CARCINOMA AND HOST LIVER

1967 ◽  
Vol 45 (2) ◽  
pp. 179-190 ◽  
Author(s):  
J. Purko ◽  
H. B. Stewart
Keyword(s):  
Nicotinic Acid ◽  
Ehrlich Ascites Carcinoma ◽  
Pyridine Nucleotide ◽  
Host Liver ◽  
Nucleotide Synthesis ◽  
Tumor Bearing ◽  
Ehrlich Ascites ◽  
Metabolic Products ◽  
Ehrlich Ascites Cells ◽  
Specific Activities

Labeled nicotinamide–adenine dinucleotide (NAD) and nicotinic acid–adenine dinucleotide (NacAD) were identified following Dowex 2 (formate) chromatography of extracts of Ehrlich ascites cells and of livers of mice 3 and 6 h after injection of nicotinamide (Nam) (500 mg/kg) containing Nam-7-14C, and 3 h after injection of nicotinic acid (Nac) (50 mg/kg) containing Nac-7-14C into tumor-bearing animals. Labeled Nac mononucleotide (NacMN) was also identified in the liver extracts. The urinary metabolic products of the precursors were separated and partially characterized. Liver appeared to be somewhat more active in synthesis of NAD than tumor; the more efficient amidation of NacAD to NAD in liver probably contributes to this difference. The results are consistent with NacAD being an intermediate in NAD biosynthesis. Investigations of extracts of acetone powders of tumor provided evidence for two possible routes of synthesis (via NMN, and NacMN–NacAD): (1) Extracts incubated with Nam mononucleotide (NMN) and ATP formed NAD. (2) Extracts incubated with Nac-14C or Nam-14C with suitable supplementation gave rise to labeled NacMN, NacAD and NAD. These substances were isolated and their specific activities determined. Glutamine appeared to enhance NAD formation at the expense of NacAD. Although a net accumulation of NAD did not occur, the formation of Nam-14C from Nac-14C and the demonstration of NADase in the preparations suggested that NAD was formed but rapidly degraded.

scholarly journals A Role for Fas in Negative Selection of Thymocytes In Vivo

1998 ◽  
Vol 187 (9) ◽  
pp. 1427-1438 ◽  
Author(s):  
Hidehiro Kishimoto ◽  
Charles D. Surh ◽  
Jonathan Sprent
Keyword(s):  
Negative Selection ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin B ◽  
Thymic Medulla ◽  
Enterotoxin B ◽  
High Doses ◽  
Specific Peptide ◽  
Selection Of

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1–100 μg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vβ8+ cells at the level of the semi-mature population of HSAhi CD4+ 8− cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vβ8+ HSAhi CD4+ 8− thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (≤1 μg) but not by high doses (100 μg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

scholarly journals Antioxidant Therapy in Graves’ Orbitopathy

2020 ◽  
Vol 11 ◽  
Author(s):  
Giulia Lanzolla ◽  
Claudio Marcocci ◽  
Michele Marinò
Keyword(s):  
Ros Generation ◽  
Related Condition ◽  
Orbital Radiotherapy ◽  
Antioxidant Agents ◽  
Graves Orbitopathy ◽  
High Doses

The balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves’ Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves’ Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here.

In vivo Anti-Tumour Activity of Ethyl Heptyloxyacetate against Ehrlich Ascites Cells

Nature ◽  
1963 ◽  
Vol 198 (4878) ◽  
pp. 384-385 ◽  
Author(s):  
GORDON F. TOWNSEND ◽  
WILLIAM H. BROWN ◽  
ETHEL E. FELAUER
Keyword(s):  
Anti Tumour Activity ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
Tumour Activity

scholarly journals Regulation of NAD Synthesis by the Trifunctional NadR Protein of Salmonella enterica

2005 ◽  
Vol 187 (8) ◽  
pp. 2774-2782 ◽  
Author(s):  
Julianne H. Grose ◽  
Ulfar Bergthorsson ◽  
John R. Roth
Keyword(s):  
Missense Mutations ◽  
Wild Type ◽  
Central Domain ◽  
Terminal Domain ◽  
Binding Residue ◽  
Nicotinamide Mononucleotide ◽  
Nad Synthesis ◽  
Default State ◽  
Regulatory Effects

ABSTRACT The three activities of NadR were demonstrated in purified protein and assigned to separate domains by missense mutations. The N-terminal domain represses transcription of genes for NAD synthesis and salvage. The C-terminal domain has nicotinamide ribose kinase (NmR-K; EC 2.7.1.22) activity, which is essential for assimilation of NmR, converting it internally to nicotinamide mononucleotide (NMN). The central domain has a weak adenylyltransferase (NMN-AT; EC 2.7.7.1) activity that converts NMN directly to NAD but is physiologically irrelevant. This central domain mediates regulatory effects of NAD on all NadR activities. In the absence of effectors, pure NadR protein binds operator DNA (the default state) and is released by ATP (expected to be present in vivo). NAD allows NadR to bind DNA in the presence of ATP and causes repression in vivo. A superrepressor mutation alters an ATP-binding residue in the central (NMN-AT) domain. This eliminates NMN-AT activity and places the enzyme in its default (DNA binding) state. The mutant protein shows full NmR kinase activity that is 10-fold more sensitive to NAD inhibition than the wild type. It is proposed that NAD and the superrepressor mutation exert their effects by preventing ATP from binding to the central domain.

scholarly journals Hydroxyethyl Starches

2009 ◽  
Vol 111 (1) ◽  
pp. 187-202 ◽  
Author(s):  
Martin Westphal ◽  
Michael F. M. James ◽  
Sibylle Kozek-Langenecker ◽  
Reto Stocker ◽  
Bertrand Guidet ◽  
...  
Keyword(s):  
Tissue Storage ◽  
High Doses ◽  
First And Second Generation ◽  
New Generation ◽  
Clinical Potential ◽  
The Impact ◽  
Hydroxyethyl Starches ◽  
Lower Molar

With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.

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